1. Field of the Invention
The present invention relates to cultivation of a cell or tissue in the fields of regeneration medicine and tissue engineering, and relates to a method of three dimensional tissue cultivation for a three dimensional tissue and or organ regeneration. Concretely, the above cultivating method is executed with any of a cell, a cell scaffold and an ECM (extracellular matrix) that a cell generates, as a cell construct. There may be a case where the above cultivating method is executed with addition of a culture fluid, other additives, a growth factor, a chemical and so on.
In short, the cultivating method of the present invention differs from the conventional static cultivation. The cultivating method of the present invention is a method relating to three dimensional cultivation where physical action is used together. The cultivating method is for realizing objective regeneration tissue by differentiation induction or dedifferentiation deterrence along with that growth, cell migration and substance migration are promoted to improve survivability of a cell by stimulating a cell of a cell construct aggressively and displacing a cell construct.
2. Description of the Related Art
For cultivation of a cell or tissue, a method of imparting physical stimulation such as pressure and tension to a cell or tissue to be cultivated is studied, and various bioreactors and so on are suggested. Two dimension cultivation (plane cultivation) is a cultivating method using a flat bottomed culture carrier, and in general, is a static cultivating method in an incubator. Suspension cultivation is a method of cultivating a non-adherent cell being suspended. This method is also a static cultivating method in an incubator. Three dimension cultivation is a method that is generally executed such that a cell scaffold where a cell is disseminated is left still in an incubator to be cultivated. It is general for the three dimension cultivation (using a bioreactor) that a cell is made to adhere to or is enclosed by a cell scaffold to process stirring of a culture fluid and so on. It is conceived that in the three dimension cultivation of a cell scaffold, physical action such as pressure, compression, tension and shear are imparted to a cell. A cultivation apparatus for imparting physical action is called “a bioreactor”, “a tissue engineering processor”, etc. This apparatus is being into practical utilization as a cell/tissue cultivation apparatus in vitro for cultivation experiments of tissue engineering and regeneration medicine.
Concerning such bioreactor having functions of cultivating a cell or tissue, and imparting physical displacement, stress and stimulation used in the cultivating, a method for cultivating a cell or tissue and an apparatus therefor are disclosed in Japanese Laid-open Patent Publication No. 2001-238663 (Abstract, etc.) as an example of using pressure and oscillation (supersonic wave), a method for in vivo, ex vivo and in vitro repair and regeneration of cartilage and collagen, and bone remodeling is disclosed in Published Japanese Translations of PCT International Publication for Patent Application No. 2004-512031 (Abstract, etc.) as an example of using pressure, a cell and tissue-cultivating apparatus is disclosed in Japanese Laid-open Patent Publication No. 2002-315566 (Abstract, etc.) as an example of using shear force, a cell and tissue-cultivating device is disclosed in Japanese Laid-open Patent Publication No. 2003-061642 (Abstract, etc.) as an example of using tensile force, a cell and tissue cultivation apparatus is disclosed in Japanese Laid-open Patent Publication No. 2003-180331 (Abstract, etc.) as an example of using compression force, a device for cultivating cell is disclosed in Japanese Laid-open Patent Publication No. H09-313166 (Abstract, etc.) as an example of using shear force, a loading device of extending and contracting stimulation for cultivating a cell by using a silicone belt is disclosed in Japanese Laid-open Patent Publication No. H10-155475 (Abstract, etc.) as an example of using tensile force, and an apparatus executing sterilization, inoculation, cultivation, preservation, transport and test of tissue and a synthetic or natural vascular graft, and a method therefor are disclosed in Published Japanese Translations of PCT International Publication for Patent Application No. H11-504216 (Abstract, etc.) as an example of using both tension and shear. A cultivating method where distortion is given to cells held on membranes by the membranes is disclosed in Japanese Laid-open Patent Publication No. 2005-143343 (Abstract, etc.). A semi-permeable membrane being used for cultivation is disclosed in International Publication Pamphlet No. WO 2006/015304 A2 (Abstract, etc.) and Published Japanese Translations of PCT International Publication for Patent Application No. 2000-513214 (Abstract, etc.). Imparting of various kinds of physical action and stimulation, and using of a semi-permeable membrane are tried for cultivation of a cell, etc.
There are regions receiving many kinds of stress in the human body. Tissue used for repairing these regions is different according to the regions. For example, a disc, a meniscus, a bone, fiber cartilage and a valve of a heart receive bending stress in vivo. This bending stress is different from simple pressure, compression, tension, shear, etc. It is unnecessary that tissue cultivated by stimulus factor such as a simple pressure, compression, tension and shear are applied to a region receiving such bending stress.
The inventors of the present invention conceives that bending is so useful for growth, etc. of a cell or tissue as stimulation or a load imparted to a cell or tissue to be cultivated. The present invention is based on such concept. Concerning this bending, there is no disclosure in the above patent documents and is no suggestion thereabout.